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This Week in Science

Ocean winds blowing harder

A large storm wave crashing into the lighthouse at the mouth of the Douro River harbor in Porto, Portugal

PHOTO: ZACARIAS PEREIRA DA MATA/SHUTTERSTOCK

Two frequently asked questions about how climate warming will affect the environment are whether windiness might change and what effects that might have on ocean waves. Young and Ribal analyzed global satellite data over the period from 1985 to 2018 to determine if there are any trends in oceanic wind speed and wave height. They found small increases in both quantities, with the strongest increases in extreme conditions and in the Southern Ocean. These findings are important for understanding air-sea exchange of energy and carbon dioxide and for projecting sea levels during storms.

Sparing T cells from inhibition

Priscilla N. Kelly

Programmed cell death 1 (PD-1) is an inhibitory receptor that normally keeps T cell immune responses in check. Immunotherapy targeting PD-1 has proven successful for certain types of cancer, but it remains unclear how PD-1 is regulated. Sugiura et al. found that a costimulatory molecule, CD80, can restrict PD-1 function during the activation of T lymphocytes. Binding of CD80 to the PD-1 ligand PD-L1 in cis on primary activated dendritic cells interfered with the ability of PD-L1 to access PD-1 on T cells, which would otherwise have inhibited T cell activation. Functional insights into PD-L1–CD80 interactions may explain the outcomes of anti–PD-1 and anti–PD-L1 cancer therapy.

Ionic floating-gate memories

Phil Szuromi

Digital implementations of artificial neural networks perform many tasks, such as image recognition and language processing, but are too energy intensive for many applications. Analog circuits that use large crossbar arrays of synaptic memory elements represent a low-power alternative, but most devices cannot update the synaptic weights uniformly or scale to large array sizes. Fuller et al. developed an integrated device, ionic floating-gate memory, that has the gate terminal of a redox transistor electrically connected to a diffusive memristor. This low-power device enabled linear and symmetric weight updates in parallel over an entire crossbar array at megahertz rates over 109 write-read cycles.

Fish catch color with rods

Sacha Vignieri

Vertebrates are typically thought to have a consistent system for processing light, in which multiple cone opsins permit color vision during the day, but a single rod opsin provides only monochrome vision in the dark. Musilova et al. analyzed more than 100 deep-sea fish genomes and found a previously unknown proliferation of rod opsin genes that generate rod opsin photopigments that are tuned to different wavelengths of light. These receptors may allow the fish to perceive bioluminescent signals that pervade their deep-sea environment. These results reveal a previously undescribed visual system that allows for color vision in the dark.

Walloping Wolbachia with quinazolines

Lindsey Pujanandez

A variety of adult parasitic worms depend on the bacterial endosymbiont Wolbachia for reproduction and survival; thus, Wolbachia is a clinical target for treating filarial nematodes. Antibiotics effective against Wolbachia require weeks of treatment and are not suitable for all patients. Bakowski et al. used a high-throughput phenotypic screen to identify quinazolines as alternative antiwolbachial compounds. The authors optimized lead compounds and showed their efficacy in multiple mouse filarial models. A short course of quinazolines could eradicate Wolbachia in preclinical filarial disease models.

Sci. Transl. Med.11, eaav3523 (2019).

Biodiversity

The state of Earth's health

Kollen Post

Biological communities, which provide critical services to humans, are greatly threatened by changes in land and sea use, direct exploitation of natural resources, climate change, and other threats. To understand what humanity is losing, we must appreciate how biodiversity contributes to human economies and culture. In an editorial, Lovejoy heralds a feat of data gathering and analysis: the first official report of the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES). This comprehensive assessment of the world's ecosystems is bleak, but the report advocates for transformational change in environmental policy by illustrating what we as a planet have already lost and what more we stand to lose.

Sci. Adv. 10.1126/sciadv.aax7492 (2019).

Biocatalysis

The right bond in the right place

Michael A. Funk

Enzymes excel at specificity because of their constrained active sites. With appropriate evolutionary pressure, they can be made to differentiate between similar substrates or between positions on a single substrate. Cho et al. used directed evolution to generate cytochrome P450 variants that target different C–H bonds in substrates, forming lactam rings of varying size (see the Perspective by Hepworth and Flitsch). The enzyme directs amidation to the desired position and simultaneously prevents other side reactions.

The path to elimination

Caroline Ash

Measles is highly infectious and can be dangerous. The classic 1968 vaccine is highly effective, and it should be possible to eliminate measles. Graham et al. found that measles transmission changes as vaccination coverage and birth rates (that is, the rate of arrival of susceptible individuals into the population) change in a country in response to socioeconomic variables. As a result, measles everywhere follows the canonical mode of decline in response to vaccination campaigns. Incidence is initially high, and variability is low. As incidence declines, variability increases, and as incidence drops toward elimination, so does variability. It is possible to identify countries that are deviating from this expectation and to adapt their vaccination programs to regain the path to elimination.

Wnt signaling out on a limb

Seth Thomas Scanlon

The Wnt/β-catenin signaling pathway is central to hematopoietic stem cell (HSC) survival, renewal, and differentiation. Both excessive and insufficient β-catenin can have adverse consequences, so “destruction complexes” ensure its precise regulation. Using a mouse forward genetic screen, Choi et al. identified a mutation in the gene limb region 1–like (Lmbr1l) that severely impaired lymphocyte development and function. LMBR1L interacted with multiple members of the Wnt/β-catenin signaling pathway. The authors found that LMBR1L works with an endoplasmic reticulum–localized ubiquitin ligase to serve as a second brake on this system in lymphocytes. Deleting β-catenin decreased apoptosis and restored proliferative capacity in an Lmbr1l-deficient mouse T cell line.

Cooperativity in synthetic gene circuits

L. Bryan Ray

Synthetic biologists would like to be able to make gene regulatory circuits that mimic key properties of eukaryotic gene regulation. Taking a cue from multimeric transcription factor complexes, Bashor et al. developed synthetic transcriptional circuits that produce nonlinear behavior from cooperativity (see the Perspective by Ng and El-Samad). Their system uses clamp proteins with multiple protein-interaction domains. Circuit behavior can be tuned by altering the number or affinities of the interactions according to a mathematical model. The authors created synthetic circuits with desired functions common in biology, for example, switch-like behavior or Boolean decision functions.

Origins of neuronal diversity

Pamela J. Hines

Although the main task of a neuroprogenitor is to produce more cells, it may not always produce the same cells. Some progenitors produce different daughter neurons as an embryo develops. Concurrently, these daughter neurons are also transitioning through states toward maturation. Telley et al. used single-cell RNA sequencing to survey the transcriptional identity of cells early in mouse brain development. As a neuroprogenitor transitioned to new states, it produced daughter neurons that reflect those new states. The neuron's own postmitotic differentiation program is apparently overlaid onto these parentally supplied programs, driving emergence of specialized neuronal cell types in the neocortex.

Mix of metabolites tunes root microbiota

Pamela J. Hines

Uncharacterized biosynthetic genes in plant genomes suggest that plants make a plethora of specialized metabolites. Huang et al. reconstructed three biosynthetic networks from the small mustard plant Arabidopsis thaliana. Promiscuous acyltransferases and dehydrogenases contributed to metabolite diversification. The plant may use these specialized metabolites to modulate the microbiota surrounding its roots. Disruption of the pathways and intervention with purified compounds caused changes in the root microbiota.

Choosing a partner

Valda Vinson

G protein–coupled receptors (GPCRs) bind ligands outside the cell and trigger events inside the cell by selectively binding and activating specific G proteins. The selectivity occurs even among highly related GPCRs. For example, five subtypes of muscarinic acetylcholine receptors (M1R to M5R) play different roles in the nervous system by binding to different G proteins. Maeda et al. determined cryo–electron microscopy structures of M1R and M2R bound to their respective G proteins. A side-by-side comparison provided a molecular understanding of G protein–coupling selectivity.

How many metals to oxidize methane?

Michael A. Funk

Methane is an important fuel, but there are few direct transformations to partially oxidized products. Bacteria use metalloenzymes to catalyze methane oxidation to methanol, a reaction of industrial interest. Understanding the metal sites that enable this reaction may inspire new biomimetic catalysts. Ross et al. used spectroscopic measurements to assign two monocopper sites in the enzyme particulate methane monooxygenase. These results differ in part from previous proposals for the location and nuclearity of the metal sites and will prompt rethinking about how this metalloenzyme catalyzes methane oxidation.

Afferents modulate newborn neurons

Peter Stern

What is the role of adult neurogenesis in learning, memory, and mood? Luna et al. found that adult-born neurons either inhibited or excited the dentate gyrus, depending on whether synaptic inputs originated from the lateral or the medial entorhinal cortex (see the Perspective by Llorens-Martín). These opposing mechanisms were driven by extrasynaptic transmission from adult-born neurons directly onto mature granule cells via metabotropic glutamate receptors or N-methyl-D-aspartate receptors, respectively. The balance between these mechanisms could explain the differences in dentate gyrus activity during two versions of an active place-avoidance task. The action of adult-born neurons thus depended entirely on the demands of the environment, which can be defined by the activity of cortical and subcortical regions sending inputs to the dentate gyrus.

Improving safety at mine tailings dams

Julia Fahrenkamp-Uppenbrink

When tailings dams containing mining wastes fail, the resulting fast-moving mudflows can be destructive and dangerous for humans and wildlife. Similar processes occur when ash ponds at power stations fail. In a Perspective, Santamarina et al. explain that although the detailed mechanisms leading to tailings dam failures are not fully understood, failures can often be traced back to substandard management and operational practices. Better monitoring and characterization during operation will help to understand and prevent future failures.

Sources of alarm in fat depots

Ifor Williams

White adipose tissue (WAT) is home to regulatory T cells and group 2 innate lymphoid cells, which are immune cells that help keep inflammation under check. Two studies now probe WAT in search of cells producing the alarm signal cytokine interleukin-33 (IL-33), which regulates these cells. Spallanzani et al. used single-cell RNA sequencing to characterize visceral WAT stromal cells and defined five distinct subtypes, with subtypes 1 to 3 producing IL-33 and subtypes 4 and 5 resembling adipocyte precursors. Mahlakõiv et al. identified adipose stem and progenitor cells as a source of IL-33 in all WAT depots and mesothelial cells as an additional source of IL-33 in visceral WAT. These studies improve our understanding of WAT stromal cell diversity and how the stromal cell landscape responds to physiological or pathological variations.

Sci. Immunol.4, eaaw3658, eaax0416 (2019).

Microrobots

Catalytic magnetic robots remove biofilm

Rachel Kline

Biofilms can cause problems in medicine ranging from catheter clogs to tooth decay. Hwang et al. applied iron oxide nanoparticles (NPs) to the task of biofilm dissolution. When mixed with hydrogen peroxide, NPs form free radicals that are bactericidal and contribute to the degradation of the biofilm matrix. A magnetic field was used to induce motion of the NPs, enabling mechanical disruption of surface biofilms. To access small spaces, the authors molded various shapes from polymer-embedded NPs. A helical structure was able to travel through catheters, and NP aggregates were tested in the root canal of extracted human teeth.

Sci. Robot.4, eaaw2388 (2019).

Cell Signaling

PC2 separates mitochondria from the ER

Wei Wong

Patients with loss-of-function mutations in polycystin (PC) 1 or 2 develop fluid-filled cysts in their kidneys because of excessive proliferation of kidney epithelial cells. Kuo et al. found that loss of the endoplasmic reticulum (ER) cation channel PC2 led to increased levels of a mitochondrial fusion factor, MFN2, and enhanced tethering of mitochondria to the ER. The increased mitochondria-ER association resulted in greater mitochondrial calcium ion influx and function, as well as cellular proliferation. These defects could be rescued by reduction of MFN2 expression in cultured cells and mouse models of polycystic kidney disease.